Biomedical subjects
Publications and source records attributed to T Kawarabayashi.
The boundary condition dependence of the critical behavior for the three dimensional Anderson transition is investigated. A strong dependence of the scaling function and the critical conductance distribution on the boundary conditions is found, while the critical disorder and critical exponent are found to be independent of the boundary conditions.
In view of the importance of amyloid beta protein accumulation in Alzheimer's disease, this paper examines age-related amyloid beta protein (Abeta) deposition and accompanying cellular changes in a mouse model in vivo. Transgenic mice were studied which expressed a gene encoding 18 residues of signal peptide and 99 residues of the carboxyl-terminal fragment (CTF) of the Abeta precursor, under the control of the cytomegalovirus enhancer/chicken beta-actin promoter. In the pancreas, Abeta accumulated in an age-dependent manner. Abeta deposits appeared as early as 3 weeks of age and increased in size and number from 4 to 16 months of age. The largest Abeta deposits were observed in the transgenic pancreas at 16 and 20 months of age. Haematoxylin and eosin staining, macrophage immunostaining, and electron microscopy showed that the Abeta fibril deposits closely correlated with degeneration of pancreatic acinar cells and macrophage activation. Abeta1-42 and Abetap3E-42 were predominant components of Abeta deposits among amino- and carboxyl-terminal modified Abeta species. These findings suggest that overproduction of Abeta causes age-related accumulation of Abeta fibrils, with accompanying cellular degeneration and macrophage activation in vivo.
OBJECTIVES: To report the clinical results of 5 fetuses after a vesicoamniotic shunting procedure (VASP). METHODS: Between 1995 and 1998, 5 patients (two with prune belly syndrome, one with a cloacal anomaly, one with urethral stenosis, and one with a sacrococcygeal teratoma) underwent VASP using a double-basket catheter. We used the following selection criteria: a fetus without chromosomal defects, with oligohydramnios, and with a predicted good renal function from sequential or single fetal urinalysis (sodium concentration, chloride concentration, and osmolarity at less than 100 mEq/L, less than 90 mEq/L, and less than 210 mOsm, respectively). RESULTS: The mean gestational age was 20.8 +/- 6.9 weeks at diagnosis, 24.2 +/- 6.0 weeks at VASP, and 30.6 +/- 6.2 weeks at delivery. In our study, 2 of 5 patients survived. One of the patients with prune belly syndrome was 18 months old at last follow-up, with hydrocephalus and a creatinine level of 0.2 mg/dL. The patient with the cloacal anomaly was 4 years old at last follow-up and had signs of clonic convulsion. However, psychomotor development was delayed in both. Of the 3 patients who died, 2 died after birth, and the autopsy determined death was due to pulmonary insufficiency. The patient with urethral stenosis died in utero. CONCLUSIONS: Although the principal purpose of VASP is to prevent pulmonary hypoplasia and dysfunctional kidneys, VASP was not always effective, as the outcomes were poor in most of our patients. A greater standardization of patient selection and a large cohort study in the future should be considered to assess VASP.
In order to clarify the distribution and pathological changes of the amyloid beta protein precursor (betaAPP), 10 Alzheimer's disease (AD) brains and seven normal control brains were examined by immunocytochemistry and in situ hybridization histochemistry. All betaAPP isoforms were distributed evenly in neuronal cell bodies and their axons and dendrites. The betaAPP-positive neuronal processes showed mesh-like networks. In AD brains, betaAPP-positive neurons and mesh-like networks were generally decreased in spite of some intensely labeled neurons. All betaAPP isoforms accumulated in neuronal processes, dystrophic neurites and senile plaques. In situ hybridization histochemistry confirmed that all isoforms of betaAPP were expressed in neurons in control brains. In AD brains, the betaAPP mRNA signal was generally decreased besides some intense signal neurons corresponding to immunostaining findings. Few astrocytes expressed betaAPP. Thus, uniform expression and distribution of betaAPP were disturbed in AD brains showing uneven decreases or increases of neuronal betaAPP expression in individual neurons and betaAPP accumulation in neurons, neuronal processes and abnormal structures including dystrophic neurites, senile plaques and neurofibrillary tangles.
A 29-year-old Japanese primipara with fetal sacrococcygeal teratoma and hydronephrosis was referred to our department at 22 weeks of gestation. The preload index of the inferior vena cava (PLI) was 0.75 and fetal cardiac failure was suspected at 28 weeks of gestation. The sodium and chloride concentrations and osmolarity of the fetal urine were 96 mEq/L, 81 mEq/L and 204 mOsm/L, respectively, and we predicted a good renal function. Then, a vesico-amniotic shunting operation was performed at 28 weeks of gestation to keep the renal function and PLI decreased 0.41 after this operation. At 30 weeks of gestation, the fetus was delivered by a cesarean section owing to preterm PROM and a huge growing sacrococcygeal teratoma. The baby was female, weighing 2,020 g, and the 1 minute Apgar score was 1. She died almost 7 hours after birth due to respiratory insufficiency. An autopsy confirmed bilateral hydronephrosis, urethral stenosis, sacrococcygeal immature teratoma, and pulmonary hypoplasia. The size of this tumor revealed 80 x 70 x 45 mm in intrapelvic cavity and 130 x 90 x 50 mm out of body, and this tumor was classified as Type II according to the American Academy of Pediatrics Surgery Section classification.
Explore the source record for details and available documents.
The hypotensive effect of adrenomedullin, a potent vasodilator peptide, was examined in conscious pregnant (6, 13 and 20 days of pregnancy) and non-pregnant rats. The intravenous administration of adrenomedullin (0.01-3.0 nmol/kg) produced a dose-dependent depressor response in pregnant and non-pregnant rats. At low doses (0.01-0.1 nmol/kg), the maximum decrease in blood pressure was significantly higher in pregnant rats (20 days pregnant) than in non-pregnant rats. At high doses, no significant difference was observed between the two groups. Furthermore, the administration of adrenomedullin did not significantly affect the basal mean blood pressure (MBP) at any dose when compared to the non-pregnant group at 6 and 13 days of pregnancy. In the ovariectomized rats, the depressor responses in 17beta-estradiol-treated, progesterone-treated and 17beta-estradiol+progesterone-treated rats were not significantly different from that in the control rats, suggesting that the augmented effect on the depressor response to adrenomedullin in pregnant rats may not be due to hormonal changes during pregnancy. The adrenomedullin receptor mRNA level of the descending thoracic aorta was significantly higher in the late-pregnancy rats (20 days of pregnancy). However, the levels did not show any difference between the early-pregnant rats (6 and 13 days of pregnancy) and the non-pregnant rats. These findings suggested that the changes in the depressor response to adrenomedullin which occur at term in pregnant rats may be mediated by changes of adrenomedullin receptor gene expression rather than by sex hormones.
BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.
We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), was infused subcutaneously into rats at a constant rate from day 14 of pregnancy to make an animal model for preeclampsia. Adrenomedullin was continuously infused intravenously at a dose of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pressure was significantly higher in the L-NAME treated rats than in the control rats. The adrenomedullin administration at day 19 of pregnancy showed a significant decrease in the blood pressure in the L-NAME treated rats than in vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedullin decreased pup mortality of the L-NAME treated rats. Adrenomedullin attenuated the L-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5-11 days of pregnancy) and in non-pregnant rats did not show any significant effect on L-NAME-induced hypertension. The adrenomedullin mRNA level was predominantly expressed at high levels in the ovary, uterus and placenta, but at low levels in other tissues in pregnant rats in late gestation. The adrenomedullin mRNA level of the L-NAME treated rats in placenta decreased more than in the normal pregnant rats in late gestation (P < 0.05). These findings suggest that the adrenomedullin might play an important role in the regulation of the cardiovascular system of the mother and fetoplacental unit in rats.
To clarify the role of presenilin-1 (PS-1) in the pathology of Alzheimer's disease (AD), we tested four antisera to PS-1. The specific antisera to the N-terminus (HSN-2) and C-terminus (HS-C) of PS-1 detected a 44/40kD holoprotein, a 25kD N-terminal fragment (NTF) and a 16kD C-terminal fragment (CTF) of PS-1 in COS-7 cells. The 25kD NTF and 16kD CTF were observed in human brains, and their amounts were not significantly different between the control and AD brains. The antibody HS-C labeled extensive neurofibrillary tangles, dystrophic neurites and curly fibers in the AD brains. In the paired helical filament (PHF) fraction containing A68 protein from AD brains, a smear pattern of CTFs was revealed. Antisera (HS-L292 and HS-L300) to cleavage sites of PS-1 also revealed immunoreactive neurofibrillary tangles in the AD brain sections and the smear pattern of CTFs of A68 protein fraction. The CTFs of PS-1 accumulate with PHF tau, suggesting a close relationship between PS-1 and cytoskeletal abnormalities in AD brains.
We investigated the usefulness of intravascular ultrasound (IVUS)-guided balloon angioplasty for in-stent restenosis in 37 lesions of 34 consecutive patients. We divided these patients into two groups: a group in which the balloon size was determined by quantitative coronary angiography (QCA group; 17 patients, 19 lesions) and a group in which the balloon size was determined by IVUS (IVUS group; 17 patients, 18 lesions). We compared short-term and 6-month outcomes for these groups. In the IVUS group, we used a balloon of a size equal to 95% of the media-to-media diameter at the distal to the stent, as determined by IVUS. No significant differences were observed in patient or lesion characteristics between the two groups. The clinical success rate was 100% in both groups, and no clinical events were observed in either of the groups. The balloon/artery ratio was larger in the IVUS group than in the QCA group (1.33 +/- 0.35 vs. 1.16 +/- 0.13, P < 0.05), and the recurrent restenosis rate was lower (17% vs. 53%, P < 0.05). These results suggest that repeat balloon angioplasty using a balloon size determined by IVUS is useful for in-stent restenosis. Cathet. Cardiovasc. Intervent. 47:298-303, 1999.
The properties of hyperpolarization-activated current in pregnant rat uterus (17-19 days gestation) were investigated using microelectrode and patch-clamp techniques, and isometric tension recording. The resting membrane potentials were -58.4 mV and -48.5 mV in longitudinal and circular muscle cells, respectively. Application of hyperpolarizing current pulses produced a time-dependent anomalous inward rectification of membrane potential only in circular muscle cells. Under voltage-clamp conditions, inward currents (Ih) were activated by long hyperpolarizing pulses below -60 mV in circular but not in longitudinal muscle cells. Application of extracellular but not intracellular Cs+ reduced the amplitude of I(h) in a concentration-dependent manner (an IC50( of 0.15 mM). The reversal potential for Ih was -26.2 mV and the slope conductance was 5 nS/pF. Changes in [K+]o and [Na+]o shifted the reversal potential, and Ih amplitude increased with excess [K+]o and decreased with low [Na+]o. The steady-state activation of Ih was well fitted by a Boltzmann equation with a half-activation potential of -84.3 mV and a slope factor of 9.6 mV. Time courses of activation and deactivation of the current strongly depended on membrane potential, and were well fitted by a single exponential function. The activation time constant of Ih was dependent on temperature. In isometric tension recording, application of extracellular Cs+ to the circular muscles reduced the frequency, but not the amplitude, of spontaneous contractions in a concentration-dependent manner. It is concluded that in pregnant rat uterus Ih channels are predominantly distributed in smooth muscle cells from the circular layer. Since Ih is activated at the resting membrane potential, it is likely that this current contributes to the maintenance of resting membrane potential and spontaneous activity in circular smooth muscle cells of late pregnant rats.
OBJECTIVE: Our purpose was to compare the functional roles of oxytocin in term and preterm labor in rats by both biochemical and pharmacologic means. STUDY DESIGN: We determined the myometrial oxytocin receptor density and the maternal plasma concentrations of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on the initiation of both term and preterm labor. RESULTS: The number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366,509 delayed the initiation of labor in rats with term and preterm labor in a dose-dependent manner. CONCLUSION: It is confirmed biochemically and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor.
OBJECTIVE: To assess the diffusion of gonadotropin into the follicular fluid (FF) and its relation to the results achieved in a human IVF-ET program. DESIGN: Retrospective pharmacokinetic study. SETTING: Fukuoka University Hospital, Japan. PATIENT(S): Eighty-seven infertile patients underwent 137 cycles of IVF-ET. INTERVENTION(S): Serum and FF were collected at the time of oocyte recovery. The hCG ratio (between follicular hCG and serum hCG concentrations, measured by time-resolved fluoroimmunoassay) was evaluated as an index of the diffusion of exogenous gonadotropin. MAIN OUTCOME MEASURE(S): Relation between hCG ratio and the results and outcome of the IVF-ET program. RESULT(S): The hCG ratio decreased with the total dosage of hMG and increased with the serum E2 level, the number of oocytes recovered, and the number of oocytes fertilized. Patients with a poor response showed a low hCG ratio, which was associated with a complete lack of fertilization. The mean hCG ratio in the pregnant cycles was significantly higher than that in the nonpregnant cycles. An hCG ratio > 0.46 was seen in all pregnant cycles. CONCLUSION(S): The diffusion of exogenous gonadotropin into the FF may be an important predictor of IVF outcome.
Carcinosarcoma of the uterus is a highly aggressive neoplasm. However, the angiogenesis of this neoplasm is still unknown. This is the first study to examine the differences in angiogenesis between the epithelial and mesenchymal elements of this biphasic neoplasm. Surgical specimens from 21 primary uterine carcinosarcomas were histopathologically evaluated, and then immunohistochemically analyzed for tumor angiogenesis, using an anti-vascular endothelial growth factor (VEGF) antibody. The microvessel density (MVD) was also measured in each element of these neoplasms, using anti-CD34 monoclonal antibody. The MVD in the epithelial element was found to be higher than that of the mesenchymal element in 20 of 21 (95.2%) primary tumors. The epithelial elements showed a higher MVD (mean, 81.6 +/- 41.1) than the mesenchymal elements (mean, 36.7 +/- 23.8) in these primary tumors (P < .0001). Moreover, the epithelial elements showed a higher VEGF expression (mean, 0.78 +/- 0.23) than the mesenchymal elements (mean, 0.37 +/- 0.20) (P < .0001). The tumors with lymph-vascular invasion showed a higher VEGF expression (n = 17; mean, 0.85 +/- 0.17) than the tumors without lymph-vascular invasion (n = 4, mean, 0.47 +/- 0.12) (P < .01). Microscopically, neither lymph-vascular space invasion nor metastatic tumors consisted of sarcoma alone in this series. In addition, a decrease in the VEGF expression was found in the transitional areas between carcinomatous and sarcomatous elements in all 10 homologous and 4 heterologous tumors evaluated. These results suggest that the tumor angiogenesis in the epithelial element may be more active than that of the mesenchymal element and also substantiated the high metastatic potential of the epithelial element in uterine carcinosarcoma. Based on these findings, carcinoma cells thus may play a key role in the angiogenesis of this biphasic neoplasm.
Endometrial specimens of 34 (25 premenopausal and 9 postmenopausal) breast cancer patients receiving tamoxifen were immunohistochemically examined using estrogen receptor (ER), progesterone receptor (PR), Ki-67, and epidermal growth factor receptor (EGFR) antibodies. Proliferative (n = 6), secretory (n = 9), and postmenopausal (n = 6) endometria served as controls. The ER and PR expressions of the glandular cells in tamoxifen-treated patients did not differ from those of the glandular cells in the control women regardless of menopausal status. The Ki-67 index of glandular cells in tamoxifen-induced amenorrheic women was found to be lower than that of the proliferative glandular cells in the control women (p < 0.03), whereas the Ki-67 index of glandular cells in the tamoxifen-treated postmenopausal patients was higher than that of the glandular cells in the control women (p < 0.02). No EGFR overexpression was found in the glandular cells of the tamoxifen-treated premenopausal patients, but expression of EGFR was high in glandular cells of the tamoxifen-treated postmenopausal patients associated with a high Ki-67 index. In competition with ovarian estrogen secretion, tamoxifen may have an antiestrogenic effect on the endometrium, but tamoxifen probably has an estrogenic effect in the absence of ovarian estrogen secretion. This estrogenic effect of tamoxifen may be associated with an EGFR autocrine system.
The adrenomedullin (AM) peptide and the expression of AM messenger RNA (mRNA) from feto-maternal tissues of 22 normotensive pregnant women and from 7 women with pregnancy-induced hypertension (PIH) during third-trimester were examined to clarify the pathophysiological features of PIH. Samples of the placenta, uterine muscle, umbilical artery, and fetal membranes were obtained from each patients under informed consent. The AM peptide was measured by a radioimmunoassay and the AM mRNA level was analyzed by Northern hybridization. The total immunoreactive AM (fmol/mg wet tissue) was significantly increased in the fetal membranes (1.95+/-0.20 vs. 3.03+/-0.44) and the umbilical artery (0.11+/-0.01 vs. 0.15+/-0.02) of the patients with PIH. On the other hand, the AM mRNA level was higher in the umbilical artery, and lower in the fetal membranes in the patients with PIH. The present results thus suggest that the changes in the expression of AM in fetal membrane and umbilical artery in PIH may play an important role in the fetal and maternal circulation.
The sensory neuropeptide substance P is known to be involved in neurogenic inflammation. We examined the effect of substance P on neutrophil adhesion to human umbilical vein endothelial cells (HUVEC). Stimulation of HUVEC with substance P increased their adhesion to neutrophils in a time- and concentration (10(-10)-10(-7) M)-dependent manner. The adhesion was inhibited by the tachykinin NK1 receptor antagonist (+)-(2S,3S)-3-(2-Methoxybenzylamino)-2-phenylpiperidine (CP-99,994) and also by the protein kinase C inhibitors 1-(5-Isoquinolinesulfonyl)-2-methyl piperazine (H-7) and bisindolylmaleimide (BIM), but not by the protein kinase A inhibitor N-12-(p-Bromocinnamylamino) ethyl]-S-isoquinoline sulfonamide (H-89). These results indicate that substance P induces adhesion of neutrophils to HUVEC by activation of protein kinase C via the NK1 receptor on the HUVEC.